Dosulepin
Identification
- Summary
Dosulepin is a tricyclic antidepressant commonly used only in patients for whom alternative therapies are ineffective due to its toxicity potential.
- Generic Name
- Dosulepin
- DrugBank Accession Number
- DB09167
- Background
Dosulepin (INN, BAN) formerly known as dothiepin (USAN), is a tricyclic antidepressant with anxiolytic properties that is used in several European and South Asian countries, as well as Australia, South Africa, and New Zealand. It is not FDA-approved due to low therpeutic index and significant toxicity in overdose. Dosulepin inhibits the reuptake of biogenic amines, increasing available neurotransmitter levels at the synaptic cleft. The use of dosulepsin is only recommended in patients who are intolerant or unresponsive to alternative antidepressant therapies. Dosulepsin is a thio derivative of Amitriptyline with a similar efficacy to that of Amitriptyline, and also exhibits anticholinergic, antihistamine and central sedative properties 8. Its hydrochloride form is a common active ingredient in different drug formulations.
- Type
- Small Molecule
- Groups
- Approved
- Structure
- Weight
- Average: 295.44
Monoisotopic: 295.139470854 - Chemical Formula
- C19H21NS
- Synonyms
- (3E)-3-dibenzo[b,e]thiepin-11(6H)-ylidene-N,N-dimethylpropan-1-amine
- 11-(3-Dimethylaminopropylidene)-6,11-dihydrodibenzo(b,e)thiepin
- Dosulepin
- Dosulepina
- Dosulépine
- Dosulepinum
- Dothiepin
- trans-dothiepin
Pharmacology
- Indication
Indicated in the treatment of symptoms of depressive illness, especially where an anti-anxiety effect is required.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Anxiety •••••••••••• ••••••• •••• •••••• Treatment of Depression •••••••••••• ••••••• •••• •••••• Treatment of Depression •••••••••••• •••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Dosulepin is a tricyclic antidepressant that interacts with various receptors and transporters. It is a monoamine reuptake inhibitor with approximately equal potency for noradrenaline and 5-HT that increases the availability of these neurotransmitters at the central synapses 8. The metabolites of dosulepin are shown to inhibit 5HT uptake by the human blood platelet 2.
- Mechanism of action
By binding to noradrenaline transporter (NAT) and serotonin transporter (SERT) in an equipotent manner and inhibiting the reuptake activity, dosulepin increases the free levels of noradrenaline and 5HT at the synaptic cleft. It is shown that the main metabolite northiaden is a more potent inhibitor of noradrenaline uptake than the parent drug 5.
Dosulepin displays affinity towards α2-adrenoceptors and to a lesser extent, α1-adrenoceptors 4. Inhibition of presynaptic α2-adrenoceptors by dosulepin facilitates noradrenaline release and further potentiates the antidepressant effects 5. It also downregulates central β-adrenoceptors by causing a decline in the number of receptors and reduces noradrenaline-induced cyclic AMP formation 7,5. Dosulepin binds to 5HT1A and 5HT2A receptors in the cerebral cortex and hippocampus as an antagonist. 5HT1A receptors are autoreceptors that inhibit 5HT release and 5HT2A receptors are Gi/Go-coupled receptors that reduces dopamine release upon activation 6. Antagonism at 5HT2A receptors may also improve sleep patterns. Dosulepin also binds to muscarinic acetylcholine receptors and causes antimuscarinic side effects such as dry mouth. By acting as an antagonist at histamine type 1 (H1) receptors, dosulepin mediates a sedative effect.
Main metabolites northiaden, dothiepin sulphoxide and northiaden sulphoxide may also bind to 5HT, α2 and H1 receptors, although with less affinity compared to the parent drug 3.
Target Actions Organism A5-hydroxytryptamine receptor 1A antagonistHumans A5-hydroxytryptamine receptor 2A antagonistHumans AHistamine H1 receptor antagonistHumans AMuscarinic acetylcholine receptor M1 antagonistHumans AMuscarinic acetylcholine receptor M2 antagonistHumans AMuscarinic acetylcholine receptor M3 antagonistHumans AMuscarinic acetylcholine receptor M4 antagonistHumans AMuscarinic acetylcholine receptor M5 antagonistHumans AAlpha-2 adrenergic receptors antagonistHumans AAlpha-1 adrenergic receptors antagonistHumans ASodium-dependent noradrenaline transporter inhibitorHumans ASodium-dependent serotonin transporter inhibitorHumans - Absorption
Dosulepin is well absorbed from the intestines to reach the peak plasma concentration of 37.6ng/mL at 2.18 hours (Tmax) following oral administration of 25mg 7. The steady state concentrations are variable among individuals due to dynamic relationship between the drug dose and plasma concentration 8.
- Volume of distribution
The mean apparent Vd is approximately 45 L/kg after oral administration of 75mg dosulepin 2. It crosses the blood-brain barrier to mediate its antidepressant actions and also crosses the placental barriers, with low concentration of the drug excreted in breast milk 8.
- Protein binding
Approximately 84% of unchanged drug is bound to serum protein 8.
- Metabolism
Dosulepin undergoes extensive hepatic metabolism, to form main metabolites N-demethylated derivative northiaden (desmethyldosulepin or northiaden) and dosulepin S-oxide. Northiaden S-oxide is among 12 basic metabolites that are found in urine. The metabolic pathways of dosulepin is thought to involve N-demethylation, S-oxidation and glucuronic acid conjugation 8.
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- Route of elimination
Dosulepin is predominantly cleared via renal elimination, mainly in the form of metabolites. Renal excretion of dosulepin and its metabolites accounts for 50% - 60% of total elimination, and biliary/fecal excretion is about 15%-40% 7.
- Half-life
The elimination half life is approximately 20.4 hours following oral administration of 25mg dosulepin 7.
- Clearance
Oral clearance is approximately 1.36 L/kg * hr following a single oral dose of 75mg dosulepin 2.
- Adverse Effects
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- Toxicity
High mortality is associated with overdose of dosulepin (>5mg/kg) with the onset of toxicity occuring within 4-6 hours. Dosulepin may increase the risk of cardiovascular toxicity (cardiac arrhythmias, conduction disorders, cardiac failure and circulatory collapse) and severe hypotension, especially in the elderly 7. Withdrawal symptoms are reported in case of sudden cessation of therapy, which include insomnia, irritability, headache, nausea, giddiness, panic-anxiety, extreme motor restlessness and excessive perspiration. There have been reports of increased suicidal thoughts or behaviour with dosulepin treatment. Oral lowest published toxic dose (Toxic Dose Low, TDLo) is 90 mg/kg in infants and 4.5 mg/kg in female adults. Intravenous LD50 in mouse is 31 mg/kg MSDS.
Most common adverse effects involve the central nervous system (drowsiness, extrapyramidal symptoms, tremor, confusional states, disorientation, dizziness, paraesthesia, alterations to EEG patterns), anticholinergic effects (dry mouth, sweating, urinary retention), cardiovascular system (hypotension, postural hypotension, tachycardia, palpitations, arrhythmias, conduction defects), endocrine system (altered libido), gastrointestinal system (nausea, vomiting, constipation) and blurred vision 8.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Dosulepin is combined with 1,2-Benzodiazepine. Abametapir The serum concentration of Dosulepin can be increased when it is combined with Abametapir. Abatacept The metabolism of Dosulepin can be increased when combined with Abatacept. Abiraterone The metabolism of Dosulepin can be decreased when combined with Abiraterone. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Dosulepin. - Food Interactions
- Not Available
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Dosulepin hydrochloride 3H0042311V 897-15-4 XUPZAARQDNSRJB-SJDTYFKWSA-N - International/Other Brands
- Depropin (CCM Duopharma Biotech) / Dopress (Mylan) / Dothip (Micro Synapse) / Dothitab (Psycorem) / Dotopine (Shou Chan) / Elate (Crescent) / Espin (Taejoon Pharm) / Harmomed (Kwizda) / Othtric (Cubit) / Prothiaden (Abbott / Teofarma) / Qualiaden (Quality Pharm) / Singsong (Yuan Chou) / Thaden (Pharmacare) / Vick-Thiaden (Vickmans)
Categories
- ATC Codes
- N06AA16 — Dosulepin
- Drug Categories
- Adrenergic Agents
- Adrenergic Uptake Inhibitors
- Agents producing tachycardia
- Agents that produce hypertension
- Agents that reduce seizure threshold
- Anticholinergic Agents
- Antidepressive Agents
- Antidepressive Agents, Tricyclic
- Central Nervous System Agents
- Central Nervous System Depressants
- Combined Inhibitors of Serotonin/Norepinephrine Reuptake
- Cytochrome P-450 CYP1A2 Inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors (moderate)
- Cytochrome P-450 CYP2B6 Substrates
- Cytochrome P-450 CYP2B6 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 inhibitors (strength unknown)
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (moderate)
- Cytochrome P-450 CYP2D6 Inhibitors (weak)
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP2D6 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Dibenzothiepins
- Heterocyclic Compounds, Fused-Ring
- Histamine Antagonists
- Histamine H1 Antagonists
- Membrane Transport Modulators
- Muscarinic Antagonists
- Narrow Therapeutic Index Drugs
- Nervous System
- Neurotoxic agents
- Neurotransmitter Agents
- Neurotransmitter Uptake Inhibitors
- Non-Selective Monoamine Reuptake Inhibitors
- Potential QTc-Prolonging Agents
- Psychoanaleptics
- Psychotropic Drugs
- QTc Prolonging Agents
- Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome
- Serotonin 5-HT1 Receptor Antagonists
- Serotonin 5-HT1A Receptor Antagonists
- Serotonin 5-HT2 Receptor Antagonists
- Serotonin 5-HT2A Receptor Antagonists
- Serotonin Agents
- Serotonin Modulators
- Serotonin Receptor Antagonists
- Sulfur Compounds
- Tertiary amine tricyclic antidepressants
- Thiepins
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as dibenzothiepins. These are compounds containing a dibenzothiepin moiety, which consists of two benzene connected by a thiepine ring.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Benzothiepins
- Sub Class
- Dibenzothiepins
- Direct Parent
- Dibenzothiepins
- Alternative Parents
- Alkylarylthioethers / Benzenoids / Trialkylamines / Organopnictogen compounds / Hydrocarbon derivatives
- Substituents
- Alkylarylthioether / Amine / Aromatic heteropolycyclic compound / Aryl thioether / Benzenoid / Dibenzothiepin / Hydrocarbon derivative / Organic nitrogen compound / Organonitrogen compound / Organopnictogen compound
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- dothiepin (CHEBI:36803)
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- W13O82Z7HL
- CAS number
- 113-53-1
- InChI Key
- PHTUQLWOUWZIMZ-GZTJUZNOSA-N
- InChI
- InChI=1S/C19H21NS/c1-20(2)13-7-11-17-16-9-4-3-8-15(16)14-21-19-12-6-5-10-18(17)19/h3-6,8-12H,7,13-14H2,1-2H3/b17-11+
- IUPAC Name
- dimethyl({3-[(2E)-9-thiatricyclo[9.4.0.0³,⁸]pentadeca-1(15),3,5,7,11,13-hexaen-2-ylidene]propyl})amine
- SMILES
- CN(C)CC\C=C1/C2=CC=CC=C2CSC2=CC=CC=C12
References
- General References
- Lancaster SG, Gonzalez JP: Dothiepin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness. Drugs. 1989 Jul;38(1):123-47. [Article]
- Maguire KP, Burrows GD, Norman TR, Scoggins BA: Metabolism and pharmacokinetics of dothiepin. Br J Clin Pharmacol. 1981 Sep;12(3):405-9. [Article]
- Fulton A, Norman TR, Cheng H, Burrows GD: Assessment of the antidepressant activity of dothiepin and its metabolites by preclinical tests. J Affect Disord. 1982 Sep;4(3):261-9. [Article]
- Gillman PK: Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol. 2007 Jul;151(6):737-48. Epub 2007 Apr 30. [Article]
- Heal D, Cheetham S, Martin K, Browning J, Luscombe G, Buckett R: Comparative pharmacology of dothiepin, its metabolites, and other antidepressant drugs Drug Development Research. 1992 May 1;27(2):121–135. [Article]
- 45. (2012). In Rang and Dale's Pharmacology (7th ed., pp. 559). Edinburgh: Elsevier/Churchill Livingstone. [ISBN:978-0-7020-3471-8]
- Co-pharma Ltd. SUMMARY OF PRODUCT CHARACTERISTICS: Dosulepin hydrochloride tablets [Link]
- Alphapharm: DOTHEP (Dothiepin hydrochloride) Product information [Link]
- External Links
- KEGG Drug
- D07872
- PubChem Compound
- 5284550
- PubChem Substance
- 310265076
- ChemSpider
- 4447605
- 3634
- ChEBI
- 36803
- ChEMBL
- CHEMBL1492500
- ZINC
- ZINC000000020249
- Wikipedia
- Dosulepin
- MSDS
- Download (599 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count Not Available Completed Not Available Depressive Episodes 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral Capsule Oral 25 MG Pill Tablet, film coated - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 131- 134.6 MSDS boiling point (°C) 339.8- 341.6 MSDS water solubility Partly miscible MSDS - Predicted Properties
Property Value Source Water Solubility 0.000572 mg/mL ALOGPS logP 4.98 ALOGPS logP 4.52 Chemaxon logS -5.7 ALOGPS pKa (Strongest Basic) 9.76 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 1 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 3.24 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 104.59 m3·mol-1 Chemaxon Polarizability 34.57 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0f6t-0090000000-866fdc86f1e3621cada4 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-1090000000-7b40f8137a87d1b068ed Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0udi-1090000000-52c87a903497bc2c4571 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-0090000000-7debc4af2cfd1efcfa86 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-00di-0290000000-c793130d7223e627858f Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-5590000000-a4f25891d1f51c65b6e2 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 181.5169306 predictedDarkChem Lite v0.1.0 [M-H]- 167.1736 predictedDeepCCS 1.0 (2019) [M+H]+ 182.2414306 predictedDarkChem Lite v0.1.0 [M+H]+ 169.5316 predictedDeepCCS 1.0 (2019) [M+Na]+ 181.6357306 predictedDarkChem Lite v0.1.0 [M+Na]+ 175.62474 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Serotonin receptor activity
- Specific Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers...
- Gene Name
- HTR1A
- Uniprot ID
- P08908
- Uniprot Name
- 5-hydroxytryptamine receptor 1A
- Molecular Weight
- 46106.335 Da
References
- Fulton A, Norman TR, Cheng H, Burrows GD: Assessment of the antidepressant activity of dothiepin and its metabolites by preclinical tests. J Affect Disord. 1982 Sep;4(3):261-9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Virus receptor activity
- Specific Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodop...
- Gene Name
- HTR2A
- Uniprot ID
- P28223
- Uniprot Name
- 5-hydroxytryptamine receptor 2A
- Molecular Weight
- 52602.58 Da
References
- Fulton A, Norman TR, Cheng H, Burrows GD: Assessment of the antidepressant activity of dothiepin and its metabolites by preclinical tests. J Affect Disord. 1982 Sep;4(3):261-9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Histamine receptor activity
- Specific Function
- In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamin...
- Gene Name
- HRH1
- Uniprot ID
- P35367
- Uniprot Name
- Histamine H1 receptor
- Molecular Weight
- 55783.61 Da
References
- Gillman PK: Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol. 2007 Jul;151(6):737-48. Epub 2007 Apr 30. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Phosphatidylinositol phospholipase c activity
- Specific Function
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
- Gene Name
- CHRM1
- Uniprot ID
- P11229
- Uniprot Name
- Muscarinic acetylcholine receptor M1
- Molecular Weight
- 51420.375 Da
References
- Gillman PK: Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol. 2007 Jul;151(6):737-48. Epub 2007 Apr 30. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- G-protein coupled acetylcholine receptor activity
- Specific Function
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
- Gene Name
- CHRM2
- Uniprot ID
- P08172
- Uniprot Name
- Muscarinic acetylcholine receptor M2
- Molecular Weight
- 51714.605 Da
References
- Gillman PK: Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol. 2007 Jul;151(6):737-48. Epub 2007 Apr 30. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Receptor activity
- Specific Function
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
- Gene Name
- CHRM3
- Uniprot ID
- P20309
- Uniprot Name
- Muscarinic acetylcholine receptor M3
- Molecular Weight
- 66127.445 Da
References
- Gillman PK: Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol. 2007 Jul;151(6):737-48. Epub 2007 Apr 30. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Guanyl-nucleotide exchange factor activity
- Specific Function
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
- Gene Name
- CHRM4
- Uniprot ID
- P08173
- Uniprot Name
- Muscarinic acetylcholine receptor M4
- Molecular Weight
- 53048.65 Da
References
- Gillman PK: Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol. 2007 Jul;151(6):737-48. Epub 2007 Apr 30. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Phosphatidylinositol phospholipase c activity
- Specific Function
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
- Gene Name
- CHRM5
- Uniprot ID
- P08912
- Uniprot Name
- Muscarinic acetylcholine receptor M5
- Molecular Weight
- 60073.205 Da
References
- Gillman PK: Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol. 2007 Jul;151(6):737-48. Epub 2007 Apr 30. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Thioesterase binding
- Specific Function
- Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazo...
Components:
Name | UniProt ID |
---|---|
Alpha-2A adrenergic receptor | P08913 |
Alpha-2B adrenergic receptor | P18089 |
Alpha-2C adrenergic receptor | P18825 |
References
- Heal D, Cheetham S, Martin K, Browning J, Luscombe G, Buckett R: Comparative pharmacology of dothiepin, its metabolites, and other antidepressant drugs Drug Development Research. 1992 May 1;27(2):121–135. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Protein heterodimerization activity
- Specific Function
- This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Components:
Name | UniProt ID |
---|---|
Alpha-1A adrenergic receptor | P35348 |
Alpha-1B adrenergic receptor | P35368 |
Alpha-1D adrenergic receptor | P25100 |
References
- Heal D, Cheetham S, Martin K, Browning J, Luscombe G, Buckett R: Comparative pharmacology of dothiepin, its metabolites, and other antidepressant drugs Drug Development Research. 1992 May 1;27(2):121–135. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Norepinephrine:sodium symporter activity
- Specific Function
- Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
- Gene Name
- SLC6A2
- Uniprot ID
- P23975
- Uniprot Name
- Sodium-dependent noradrenaline transporter
- Molecular Weight
- 69331.42 Da
References
- Gillman PK: Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol. 2007 Jul;151(6):737-48. Epub 2007 Apr 30. [Article]
- Wille SM, Cooreman SG, Neels HM, Lambert WE: Relevant issues in the monitoring and the toxicology of antidepressants. Crit Rev Clin Lab Sci. 2008;45(1):25-89. doi: 10.1080/10408360701713112 . [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Serotonin:sodium symporter activity
- Specific Function
- Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into t...
- Gene Name
- SLC6A4
- Uniprot ID
- P31645
- Uniprot Name
- Sodium-dependent serotonin transporter
- Molecular Weight
- 70324.165 Da
References
- Gillman PK: Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol. 2007 Jul;151(6):737-48. Epub 2007 Apr 30. [Article]
- Wille SM, Cooreman SG, Neels HM, Lambert WE: Relevant issues in the monitoring and the toxicology of antidepressants. Crit Rev Clin Lab Sci. 2008;45(1):25-89. doi: 10.1080/10408360701713112 . [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- Gillman PK: Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol. 2007 Jul;151(6):737-48. Epub 2007 Apr 30. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58293.76 Da
References
- Gillman PK: Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol. 2007 Jul;151(6):737-48. Epub 2007 Apr 30. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Data supporting this enzyme inhibition is limited.
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55930.545 Da
References
- Gillman PK: Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol. 2007 Jul;151(6):737-48. Epub 2007 Apr 30. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Gillman PK: Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol. 2007 Jul;151(6):737-48. Epub 2007 Apr 30. [Article]
Drug created at October 13, 2015 23:52 / Updated at May 07, 2021 21:06